ES2316778T3 - COMPOSITIONS AGAINST INFLAMMATORY PROCESSES. - Google Patents

Abstract

A composition comprising an extruded, thermally processed chicory extract, which comprises sesquiterpene lactose, comprising alpha-methylene-gamma-butyrolactone (alpha-MGBL), wherein, the chicory extract is obtained by degreasing the plant material of chicory, to form a first plant extract and, subsequently processing the first plant, using the first plant extract, using acid hydrolysis and solvent extraction, with ethyl acetate, to form the chicory extract.

Description

Compositions against inflammatory processes.

The present invention, refers, in a way general, to compositions. In a more specific way, this invention refers to compositions that include extracts Extruded, thermally processed, chicory, to improve Health, in humans and animals. Chicory contains an amount desirable and effective sesquiterpene lactones, including α-methylene- γ-butyrolactone (? -MGBL), when heated.

Background and background of the invention

The need to improve health, in mammals, has involved, and continues to involve, continuous efforts of research and discoveries, to prevent and / or treat diseases. So, for example, from an inflammation, you can appear an irritation or discomfort, in a mammal, due to example, to an inflammation in the skin, an inflammation in the eyes, an inflammation in the intestine, or the like. Further, in addition, it is believed, in a general way, the fact that, the chronic inflammation, may increase the risk of developing another disease or ailment, such as, for example, osteoarthritis, Immune disease, cancer, or the like. In this sense, it understands, in a general way, the fact that inflammation is triggered by a factor transcription activity NF? Increased, which leads to the expression of enzymes and proinflammation and inflammation receptors. One more way specific, inflammation may occur due to activity Enzymatic enzyme, in mammals, such as that consisting of an increased oxygenase activity, including the cyclooxygenase-1, the cyclooxygenase-2 and the like.

In a general way, the fact that dietitians and other nutritional sources contain a certain number of constituents or agents is known, which are believed to be capable of protecting against disease, humans and animals. Thus, for example, oligosaccharides, such as inulin, and various fructo-oligosaccharides, as reported, have prebiotic effects, such as promoting the growth of bifido- and lacto-bacteria, in the gastro-intestinal tract, to at the expense of pathogens, including, for example, Clostidium perfringens . See, for example, Gibson et al ., Food Microbiology, 11, pages 491-498 (1994). Although the majority of reported experiments have been carried out in vitro , there have been reports, in which it is said that these oligosaccharides have a similar effect, in the intestines of rats and humans. In this sense, it is known, in a general way, the fact that, the promotion of the growth of bifido- and lacto-bacteria growth, through the use of oligosaccharics, can provide a variety of beneficial effects, both in animals and in humans , such as the prevention and / or treatment of diarrhea, increased growth, improved ability to breed, or other similar beneficial effects, which improve health.

Inulin and other pathogens, which they are believed to promote health, both in humans and in animals, just as has been discussed above, above, in general, can be derived from plants or other natural sources. So, for example, it knows, in a general way, the fact that, inulin, is purifies from plants that contain high concentrations of inulin, such as chicory, Jerusalem artichoke, the Leek and asparagus. In this sense, the plant, in a way typical, purified, or otherwise, treated before use, in order to improve a plant flavor, so that it eliminate, or at least minimize, a bitter taste, typically associated with chicory. See, for example, the patent U.S. 4,864,852.

In a general way, the plant product purified, is prepared by hydrolyzing with acids or enzymes. Next, the hydrolyzate is collected and condensed, to obtain the bioactive agent, such as inulin. So by example, Japanese patent JP 63-309147, gives know the grinding of chicory tubers, hydrolyzing them partially with acids and then drying the hydrolyzate with or without neutralization. However, the purification of, by example, fructo-oligosaccharides and inulin, can greatly increase the cost of the dietary product. By consequently, the use of such types of dietary products has been limited, in a general way, to food or dietary products special, in humans and animals.

There is therefore a need, in terms of being able to have a composition that includes ingredients natural, such as thermally processed chicory and / or extracts of this, which are tasty, in humans and animals, which can be produced cheaply, and that can improve health in humans and animals, such as prevention and / or treatment of inflammation.

Summary of the Invention

The present invention relates to compositions, which are defined in the annexed claims, which can be used to prevent and / or treat inflammation The composition of the present invention, includes sesquiterpene lactones, which include             α-methylene- γ-butyrolactone (? -MGBL), derived from a chicory Extruded, thermally processed.

The applicants have demonstrated the fact of which, chicory root extracts, contain one or more photochemicals with the ability to inhibit activity enzymatic and / or transcription, in mammals, such as Enzymatic activity related to oxygenase, and the activity of transcription relative to NF-? B. The Applicants have further demonstrated the fact that thermally processed extracts of chicory roots, possess an enhanced enzyme inhibition activity, relative to the cyclooxygenase and / or enhanced inhibition, related to NF- \ kappaB. The applicants have demonstrated a relationship between the improvement of generation inhibition, during thermal processing, of an active molecular species, namely the α-methylene- γ-butyrolactone (? -MGBL).

In this sense, the fact of that, the inhibition of such type of enzymatic activity / of transcription, prevents and / or treats inflammation, in mammals. By inhibiting the inflammation process, it can be reduced the risk of incidence of another disease or ailments, such as the cancer, which is believed to result from inflammation (by example, chronic inflammation).

For this purpose, in a form of presentation of the present invention, a nutritional composition is provided, as defined in the appended claims. In a way preferably, the chicory material comprises an amount of at least a percentage corresponding to 0.5%, by weight.

The plant material, in a form of presentation, is derived from chicory.

The composition may include other agents. dietary, derived from the source of plants, in addition to photochemical agents These dietary agents may include any appropriate constituent, capable of inhibiting activity enzyme associated with cyclooxygenase. In a form of presentation, dietary agents, in addition to the Photochemical products, include antioxidants, glucosaline, Chondroitin sulfate, omega-3 fatty acids, any other appropriate dietary agents, and combinations of these.

The present invention also provides a food product for pets. The product for domestic animals, includes a starch matrix; and a quantity Effective of an extract of chicory, extruded, thermally processed, which includes sesquiterpene lactones, which include αMGBL, capable of inhibiting enzyme activity, in a mammal, to reduce a risk of inflammation.

In another form of presentation of this invention, a process for preparing a product is presented nutritious food, capable of reducing the risk of incidence of inflammation. The procedure is defined in the claims. attached. The nutritious food product includes at least one percentage of 1%, by weight, of chicory extract.

Preferably, the extract of chicory, is processed by degreasing the chicory material, to form a first chicory extract and subsequently process the first chicory extract, with ethyl acetate, via acid hydrolysis, to form the plant extract.

The present invention also provides the use of a therapeutically effective amount of a material of extruded chicory, thermally processed, in accordance with the invention, for the preparation of an intended composition to reduce the risk of inflammation in a mammal at risk of inflammation. With decreased enzyme activity, the risk of inflammation, in the mammal, can be reduced, thereby reducing a risk of other ailments or diseases, which may result from inflammation, such as osteoarthritis, the autoimmune disease, cancer, or the like.

An advantage of the present invention is that of provide an improved composition, which can be used to reduce the risk of incidence of inflammation in mammals. In this sense, the composition, is able to inhibit the activity enzymatic, whose result is believed to treat and / or prevent inflammation.

Another advantage of the present invention is that of provide an improved composition, which includes material from chicory containing one or more phytochemicals, capable of inhibit an enzymatic activity, such as that related to cyclooxygenase, which is believed to prevent and / or treat inflammation in mammals

Still another advantage of the present invention, is to provide procedures to produce compositions improved, containing one or more chicory extracts, the which can improve the flavoriness of the composition, at the same time to maintain the enzymatic inhibition properties of plant material, which are capable of reducing the risk of inflammation in mammals

Still another advantage of this invention is to provide treatment procedures and / or prevention against inflammation in mammals, which include the administration of an improved composition.

Advantages and additional features of the present invention, are described in the detailed description of the invention, which is given below, and these will result evident, following said description.

Detailed description of the drawings

Figure 1 illustrates the inhibition of COX-2 expression, in HT29 cells, by α-methylene- γ-butyrolactone  (? -MGBL), according to a form of Presentation of the present invention.

Detailed description of the present invention

The present invention relates to compositions as defined in the claims attached.

The applicants have discovered, in a way surprising, the fact that, by thermal processing, certain plants and / or plant extracts thereof, such as the chicory, photochemicals, and the like, can be generated with an improved inhibition of the enzymatic activity of cyclooxygenase and / or the enhanced transcription activity of NF-? In mammals, which is believed to be reduces the risk of inflammation, including, for example, the skin inflammation, eye inflammation, inflammation of the intestine, inflammation of the colon, and the like. In a presentation form, the enzymatic activity, is derived from the cyclooxygenase, such as cyclooxygenase-1 and / or the cyclooxygenase-2.

The applicants have demonstrated, through tests test, the fact that, extracts such as extracts of heat-processed, thermally processed plants, particularly chicory extracts can inhibit activity cyclooxygenase, as well as the transcription activity of NF- \ kappaB. In a particular way, it is believed that, chicory extracts, extruded, thermally processed, they have a more pronounced effect on the inhibition of cyclooxygenase-2, if compared with the cyclooxygenase-1. Thus, in this way, it is believed that, the inhibition of this type of enzymatic activity, reduces the inflammation in mammals It is believed that, by reducing the inflammation, the risk of incidence of others may be reduced diseases or ailments that are believed to result from inflammation, particularly, chronic levels of inflammation. The others types of diseases, may include, for example, cancer, autoimmune disease, osteoarthritis, and combinations of these.

In addition to photochemical products, such and as discussed above, above, the fact is known that, plants, such as chicory, also contain prebiotic fibers, such as oligosaccharides, including the inulin, which is believed to reduce the incidence of cancer, particularly in the colon. In this regard, the applicants, they believe that the improved benefits can be realized due to the combined effect of prebiotic fibers and phytochemicals, which can inhibit enzymatic activity, to prevent and / or treat inflammation in mammals, particularly inflammation chronic, which can cause cancer, such as cancer colon, if the inflammation remains untreated.

Applicants have also demonstrated the fact that, the enzymatic inhibition properties of the thermally processed extruded composition of the present invention, are essentially unaffected by the conditions of processed, under which, the compositions are prepared according with the present invention. Thus, for example, the purification of plant material, made in accordance with this invention, which can be used to reduce the bitterness of the plant extract and, thus, in this way, improve appetite, It has negligible effects, if any, on Nutritional properties of the resulting purified product. In In this sense, the resulting extract product may result from Raw plant extracts, such as chicory. This can eliminate the need for a purification face or other treatment by the style, of the material of plants necessary to produce the resulting bioactive fractions.

As used here, in this document, the term "bioactive", or other similar terms, such as "bioactive fractions", mean any constituent or constituents that may exhibit an activity biological, a chemical activity, or a similar activity, in a mammal or mammals, which are capable of improving health in a mammal. Examples of bioactive agents include, for example, to prebiotic fibers, photochemicals and by style.

As used here, in this document, the term "prebiotic", or other similar terms, including that of "prebiotic fibers", means a substance or constituent, which can promote growth  of microorganisms in mammals.

As used here, in this document, the term "photochemical product", or other similar terms,  including that of "photochemicals", and that of "agent photochemical "means any chemical produced by a plant, which is believed to impart health benefits, in humans and / or animals, such as prevention and / or treatment of inflammation or other similar diseases.

As used here, in this document, the term "enzymatic activity", or other terms similar, such as "enzymatic activity", mean any appropriate enzyme that can act as a catalyst, during any biological, chemical process, or by the style, which is appropriate, which is believed to effect health, in a mammal. Thus, for example, it is believed that the inhibition of Enzymatic activity related to cyclooxygenase, reduces the risk of incidence of inflammation. Thus, for example, it is believed that the inhibition of the enzyme activity related to cyclooxygenase, Reduces the risk of inflammation.

The composition, can include any types  and appropriate and compatible amounts of constituents, of such so that the composition can be used effectively, to prevent and / or treat inflammation. In a form of presentation, composition, includes an extract of chicory, which It contains one or more prebiotic fibers and photochemical agents, which they are able to inhibit enzymatic activity, such as the Enzymatic activity related to cyclooxygenase. It is believed that, This is responsible for the treatment and / or prevention of inflammation.

The fact that, the chicory, can be processed to form an extract, in a variety  in different and appropriate ways. In a general way, the root of chicory, is ground, pulverized or supplied in a way appropriate. The plant material can then be processed additionally, in a certain number of different stages, to Produce the product extract. In a form of presentation, it perform a degreasing procedure, in the plant material, to produce an extract that results from the fats removed from the plant material. The degreasing procedure can lead to carried out through any degreasing processing conditions, with any appropriate types and amounts of solvents, including, for example, hexane.

In a form of presentation, the extract resulting from the degreasing procedure, can be processed additionally, via acid hydrolysis, to produce another type of plant extract, which can be added to the composition of the present invention The acid hydrolysis process can be carried out through any processing conditions of Degrease, with any appropriate types and amounts of solvents, including, for example, ethyl acetate.

In a form of presentation, the extract from the degreasing procedure, can be processed additionally, via a solvent extraction procedure. Solvent extraction can be carried out by any processing conditions and in the presence of any appropriate amount and type of solvent. In a form of presentation, the solvent, includes a methanol solution (" MeOH ") and water, mixed in a 1: 1 ratio value, referred to volume. The solution resulting from the procedure of solvent extraction, can be further processed, by evaporation of the solvent, under conditions appropriate, to produce another extract. In an alternative way, the solution resulting from the extraction procedure with solvent, can be processed further, by evaporation of the solvent, under appropriate conditions, to produce another extract. Alternatively, the resulting solution, it can be treated via an adsorbent agent, such as the polyvinylpyrrolidone, or the like, to trap polyphenols. He treatment with adsorbent agent, can be carried out under any appropriate processing conditions. The examples specific preparation of plant extracts, in concordance with a form of presentation of this invention, are detailed below, below.

In a form of presentation, the raw material ground ground, is thermally processed. The applicants have demonstrated the fact that, in this way, the plant material, raw, which naturally contains lactones of sesquiterpene (SQLs), is enriched in an inhibitory species of COX2, highly active, namely the α-methylene- γ-butyrolactone (? -MGBL). In fact, this molecule exhibits a Improved thermal stability, compared to other SQLs. So by For example, the fact that, this molecular species, inhibits inflammatory activity, in part, through the direct interaction with the transcription factor NF-? And the inhibition of its binding to DNA. Be proposed the fact that the inhibition resulted from alkylation of a precise amino acid Cys 38, in the p65 domain of NF \ kappaB. Inhibition results in a decrease in the expression of several proinflammatory and inflammatory receptors and enzymes, among which, is the cyclooxygenase-II. The SQLs, in general, and the α-MGBL, in a particular way, inhibit the COX-2 activity and / or its expression. The appliers, have demonstrated the fact that, the α-CH 2 - γ-butyrolactone, specifically inhibits, and with great power, the activity COX-2

In a form of presentation, the fiber or fibers prebiotics and the photochemical agent or agents of the composition, They can be derived from chicory. As discussed previously, above, the applicants believe that the effect combined prebiotic fiber, and the phytochemical source of the chicory, may result in a chemoprotective effect improved, so that inflammation in mammals can be treated and / or prevented. Prebiotic fiber, may include any appropriate amount and type, including, for example, to oligosaccharides, such as inulin, and various       fructo-oligosaccharides, soy oligosaccharics,  and combinations of these.

Photochemical agents may include any appropriate type and quantity, so that these are capable of inhibiting COX-II enzyme activity or NF-? transcription activity, which is believe that they are responsible for the prevention and / or treatment of the inflammation. In a form of presentation, the photochemical agent of plant material, is able to inhibit activity cyclooxygenase, such as the activity of the cyclooxygenase-1 and / or the cyclooxygenase-2 and / or transcription activity NF- \ kappaB. It is believed that, by inhibition of the enzymatic and / or transcription activity of the products Photochemicals of the present invention, these are capable of prevent and / or treat inflammation, including, for example, the Chronic inflamation. In this sense, the risk of incidence of another disease or ailment, which is believed to be caused by inflammation, such as cancer, Osteoarthritis, autoimmune disease.

In addition to photochemical products, the Plant source, may include other dietary agents, which are capable of inhibiting enzymatic activity. In a way presentation, the dietary agent, includes antioxidants, glucosamide, chondroitin sulfate, fatty acids omega-3, similar agents, and combinations of these.

The fact that, the Composition of the present invention, may include a variety of different and appropriate ways. In a form of presentation, the composition, may include a nutritional supplement, a food preparation for humans and / or animals, a product food for pets and / or a composition Functional food, or the like. The composition can be added to the product, in any quantity that is appropriate. In a form of presentation, the food product, includes the plant material of the composition, in an amount corresponding to a percentage of at least 0.5%, by weight, preferably, in an amount corresponding to a percentage that falls within a range that they range from about 1% to about 30%, in weight, more preferably, in a corresponding amount at margins ranging from about 1%, to approximately 2%, by weight.

In another form of presentation, the compositions pharmaceuticals that contain the active ingredient α-methylene-γ-butyrolactone,  fragments or extracts that contain it, can be in any appropriate form for oral use, such as, for example, tablets, pills, aqueous or oily suspensions, materials in dispersible powder or granules, emulsions, hard capsules or soft, or syrups or elixirs. The compositions intended for the oral use, can be prepared in accordance with any procedure known in the specialized art of the art, for the manufacture of pharmaceutical compositions and, such types of compositions, may contain one or more agents selected from among the group consisting of sweetening agents, agents flavorings (condiments), coloring agents, and agents preservatives, in order to provide preparations Pharmaceutically elegant and tasty. The tablets contain the active ingredient or ingredients, in admixture, with excipients not toxic, pharmaceutically acceptable, such as diluents, granulating, disintegrating and lubricating agents, inert, which are appropriate for the manufacture of tablets. The tablets, they can be uncoated, or they can be coated by known techniques, to delay disintegration and absorption in the gastrointestinal tract and thereby provide an action held for a longer period of time. Formulations for oral use, they can also be presented as hard jellies, where, the active ingredient is mixed with water, or with a medium oily Aqueous suspensions contain the active material, in mixing with appropriate excipients, for the manufacture of aqueous suspensions, such as, for example, agents of suspension, dispersing or wetting agents, preservatives, coloring agents, flavorings (condiments), and agents sweeteners Powdered materials and dispersible granules suitable for the preparation of an aqueous suspension, by the addition of water, provide the active ingredient or active ingredients, in admixture with a dispersing agent or humectant, a suspending agent, and one or more preservatives. They may also be present, additional excipients, tale as, for example, sweetening agents, flavorings (condiments) and dyes.

In a form of presentation, the present invention, provides an animal food product domestic or company, which includes a starch matrix, and an effective amount of a composition, as defined in the appended claims. The food product for companion or domestic animals of the present invention can include any appropriate number, type and quantity of constituents, and processed in any appropriate manner, to Form a desirable product.

In a form of presentation, the present invention includes a gelatinized product, which contains a Amount of chicory extract. Chicory extract, includes at least one source of prebiotic fibers and products photochemicals, capable of inhibiting enzymatic activity, in mammals, which is believed to improve health, in mammals.

In one form of presentation, the chicory extract includes inulin, in an amount sufficient to provide at least a percentage of 0.25%, by weight, of insulin, based on dry matter. In a form of presentation, the plant materials include at least 50%, by weight, of inulin. For ease of handling, the plant material, preferably, is in crushed form, or in the form of a dried, dried matter. As described above, the procedure above uses crushed chicory and / or dried extracts thereof (dehydrated). However, it should be understood that any extract of
Appropriate chicory, in any appropriate form, and be added to the cereal product, in any appropriate amount.

As described below, below, the remaining ingredients included in the cereal product geletanized, can be any ingredients usually Used in gelatinized cereal products. Usually these ingredients, include a source of starch and a source of proteins Suitable sources of starch are, for example, cereals, such as, for example, corn, rice, wheat, beets, barley, oatmeal, soybeans, and mixtures of these. The appropriate sources of protein, can be selected from any source of animal or vegetable protein Examples of these include the meat meal, bone meal, fish meal, concentrates of soy protein, milk proteins, gluten, and the like. The choice of starch and protein sources, it will determine extensively through the nutritional needs of the  animal or human, considerations of wisdom or appetite, the type of cereal product produced, or other considerations like that. In the gelatinized cereal product, they can also incorporate several other ingredients, such as sugar, salt, spices, sauces, vitamins, minerals, agents flavorings (condiments), fats and the like, in the way that is desired.

The gelatinized cereal product, I could occur in many different ways, as desired. Do not However, for a dry cereal product (dehydrated), a form especially appropriate to produce the product, is the consisting of extrusion cooking. This can be done. in a way that is well known in the specialized art of technique. Thus, for example, in an appropriate process, a mixture of food, is introduced into a preconditioner. This mix of food, is mainly formed by a source of starch, a source of protein, and consistent plant material in chicory. In a form of presentation, chicory includes at least about a percentage of 1%, by weight, of food material, preferably, at least one percentage of approximately 2%, by weight. In a form of presentation, the amount of plant material, in the material food, is the corresponding to a percentage comprised within margins ranging from approximately 10% to about 20%, by weight, preferably, approximately 10%, by weight.

In the preconditioner, proceed to enter and mix water or steam, or both, in the food mixture. Be proceed to introduce and mix a sufficient amount of water or steam, in the food mixture, to moisten the mixture food in question. If desired, the temperature of the food mixture, can be raised, in the preconditioner, to a level corresponding to margins ranging from approximately 60 ° C to about 90 ° C, by weight. A preconditioner appropriate, is the one described in US Pat. 4,752,139. The fact that the use of the preconditioner

The food product that leaves the preconditioner, is then introduced in a extruder The extruder can be any single screw spindle extruder, or double spindle helical, and cooking. Appropriate extruders can Obtained from the firm Wenger Manufacturing Inc. Clextral SA, Bühler AG, and the like. During the passage through the extruder, the moistened food, passes through a cooking zone, in the which, it is subjected to mechanical shear, and is heated. In One form of presentation, the moistened food, is heated to a maximum temperature of up to approximately 150ºC, and in an area of conformation. The indicative pressure, in the conformation zone, is corresponding to a value within a range ranging from about 300 kPa to about 10 MPa, any way you want. If desired, water can be introduced or steam, or both, in the cooking zone. During the passage through the extruder, the starch source of the moistened food, is gelatinizes, in order to provide a matrix structure gelatinized mainly based on starch, protein and plant material consisting of chicory.

The gelatinized matrix that leaves the extruder, is forced to pass through a matrix appropriate, for example, a matrix like the one described in the European patent EP 0 665 051. From the matrix, an extrudate comes out shaped, endowed with a certain shape with a section transverse corresponding to the hole in the matrix. In dependence on the existing conditions in the extruder and the starch source used, the shapely extruded, is expands to a greater or lesser extent. The extruded endowed with shape, cut, then into pieces, using blades. TO then the pieces are dried (dehydrated) individual and, if desired, are coated with protective agents or flavorings (condiments), or both. After proceeding to chilled, the pieces can be packed in appropriate containers. From an alternative way, the individual pieces, can conform in the form of flakes, and then dried (dehydrated).

Depending on the ingredients used, The cereal product used, can be in the form of "cubes" appropriate for use as animal feed domestic or company, appropriate expanded parts or pieces for use in breakfast cereals, flakes appropriate for use in breakfast cereals, and the like.

It is also possible to produce a product of dried cereals (dehydrated), proceeding to mix together water and cereal product ingredients, for example, proceeding to mix them in a preconditioner. The wet mixture, it can then be shaped, to provide it with a desired shape, proceeding to use, for example, forming rollers of shape. The shaped, endowed mixture can then be cooked  in an oven, at any temperature level that is appropriate. In a form of presentation, the temperature, is the corresponding to a level within a range from about 220 ° C to about 280 ° C, during a appropriate cooking time. In a form of presentation, time cooking, is within a range that They range from about 10 minutes to about 1 hour. The cereal product, dried (dehydrated), has the appearance of a cooked cookie.

In case you want to produce a product simulated meat, which can be used in food for domestic or companion animals, packaged in cans, for this, Any procedure that is appropriate can be used. So, for example, the procedures may be those corresponding to those that are described in the patents US 4,781,939 and US 5,132,137. In these procedures, a protein source is emulsified, Especially a meat material. The meat material, can be any appropriate source of animal protein, including, by For example, meat from muscles or meat from of the skeleton, of mammals, by-products of poultry, of fish or of meat, such as those consisting of hearts, liver, kidneys, tongue or the like, or meat meal. The sources of proteins from cereals may also be included, in case wanted. The exact composition can be selected accordingly with the desired cost and taste. The emulsion can be carried out on any equipment that is appropriate.

The dried chicory is added (dehydrated), to the emulsion. The additional protein can be any source of protein, as mentioned above The exact choice will depend on the availability, cost, and wisdom or appetite. The additional protein, can be added in any quantity that is adequate. In one form of presentation, the additional protein can be added in an amount corresponding to percentages that are are included within a range from about 5% to about 35%, by weight.

If required or desired, the emulsion will be You can also add fat. Usually the amount of fat in the emulsion, it must be controlled, to facilitate processing, and to get an acceptable product. However, the material of meat, may contain, well, the desired amount of fat, not being necessary in this way no adjustment. In a typical way, At this stage, the emulsion contains a maximum level of fat, corresponding to a percentage of approximately 25%, by weight. In a form of presentation, the amount of fat in the emulsion, it is the corresponding one to percentages included within margins ranging from about 5% to about 15%, by weight, more preferably, from about 7% to about 12%, by weight. The relationship value, referred to mass, of the protein with respect to fat, in the emulsion, it is preferably 1: 1 to 7: 1. In case add, the fats, can be any animal fats that are appropriate, such as tallow, or these may consist of fats vegetables.

To the emulsion, ingredients can be added additional, such as sugars, salts, spices, agents flavorings (condiments), minerals, and the like. In a way presentation, the amount of additional ingredients used, is the corresponding to percentages included within margins ranging from approximately 1% to approximately 5%, by weight, of cereal product gelatinized

Water may also be added, to provide a percentage of humidity corresponding to percentages comprised within margins ranging from approximately 45% up to approximately 80%, by weight, of moisture, in the emulsion. In case an amount is present sufficient moisture, in the meat material, it is not necessary add water

Once mixed, the emulsion, in a way Preferably, it is introduced through a vacuum oven, or a similar aeration apparatus, in order to deaerate the emulsion. This one eliminates the air, which would otherwise cause a disruption of the formulated emulsified product, and would reduce its meat-like appearance. The emulsion, is introduced, to then, in an emulsion mill, which holds the emulsion, for rapid mechanical heating and shearing. May use any suitable emulsion mill, including, for example, the emulsion mill disclosed in the U.S. Patent 5,132,137. Other emulsion mills appropriate, are those that are commercially available in the market, under the trademark of TRIGONAL, and that may Obtained from the firm Siefer Machinenfabrik GmbH & Co. KG, Bahnhofstrasse 144, Postfach (post office box) 101008, Velbert 1, Germany.

The emulsion temperature can rise to the desired coagulation temperature, in the emulsion mill, in few seconds. In a form of presentation, the temperature of coagulation, is the one corresponding to a value within margins ranging from approximately 100 ° C to approximately 120 ° C. In a presentation form, the temperature of coagulation, is the one corresponding to a value within of margins ranging from approximately 45 ° C to approximately 75 ° C, as described in the patent U.S. 5,132,137. In a general way, energy mechanics generated in the emulsion mill, it will be sufficient as to heat the emulsion, to the desired temperature, but this one, can be supplemented by steam injection overheated.

The heated emulsion leaving the mill emulsion, can be transferred to the retention tube. In the tube retention, the heated emulsion, coagulates, at the same time as move slowly, along the retention tube. The time of residence or retention of the heated emulsion, in the tube retention, is enough for the emulsion to have coagulated in a firm emulsion product, after reaching the check tube outlet. Firm emulsion product comes out of the retention tube, is then transferred to a cutting blade, where, this one, is cut into pieces, such as "cubes", of an appropriate size for use in a product Food for dogs. The "cubes" or bits, have the appearance and texture of meat. The "cubes" can undergo a process for its conformation in the form of flakes. The "cubes" can also be formulated for conversion into a product of the type "cubes" in sauce. Others are also known procedures for the production of "cubes", and these can used, for example, to extrude a mixture of food, by cooking the food mixture in a steam oven and, to then cutting the cooked extrudate, turning it into bits or "cubes".

If you want to produce a food product packaged in cans, for pets or pets, in form from a meat loaf or bar, a meat shake can be prepared, proceeding to emulsify an appropriate meat material, to produce a meat emulsion. The meat material can be any appropriate meat source, for example, as it has been described above, above. The meat emulsion, it is they can add appropriate gelling agents, including gums, such as kappa-carraginine, gum carob bean, guar gum, xanthan gum, or the like. In a presentation form, a quantity of rubber is used, corresponding to a percentage that does not exceed approximately 2%, by weight, of the gum used. The material of dried chicory plant (dehydrated), is added, to then to the meat emulsion.

To the meat emulsion, they can be added additional ingredients, such as sugars, salts, species, sauces, flavoring agents (condiments), minerals, and by style. The amount of additional ingredients used is, of a preferable form, corresponding to a percentage that ascend to a value within a range that goes from about 0.25% to about 5%, by weight, of the meat shake. Water can also be added to the emulsion of meat, to provide a percentage within a few margins ranging from approximately 70% to approximately 85%, by weight. If a sufficient quantity is present of moisture, in the meat material, it is not necessary to add Water.

The meat emulsion is added, then at a temperature above about 65 ° C, in a mixer - baking oven. If desired, it can be injected Steam in the meat shake. Then proceed to emulsify again the heated meat emulsion, to provide a bread or bar shake, maintained at a temperature above a level of approximately 60 ° C, up to can filling The fact that the product should be appreciated of gelatinized cereals, can be produced by any appropriate procedure, and not only by those who have described above, above. In the cereal product gelatinized, other types of oligosaccharides can also be added, such as fructo-oligosaccharides and oligosaccharides soy. Soy oligosaccharides can be added in the form of soy flour, or in the form of any other source of soy.

The cereal product can be in any appropriate form, including, for example, the dry form (dehydrated), semi-moist and moist. However, the matrix that forms the cereal product must be gelatinized, with in order to eliminate or destroy sesquiterpene compounds that may be present in the plant material. Should appreciate the fact that, the cereal product of the present invention, can be carried out for human consumption and / or of animals.

By way of example, and not limitation, below, to food products for animals of company or domestic, made in accordance with a form of Presentation of the present invention.

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Example one

Dry food product (dehydrated), for animals of company

It proceeds to form a food mixture, to basis of approximately 58%, by weight, of corn, approximately a percentage of 6%, by weight, of corn gluten, approximately a percentage of 23%, by weight, of meat, being formed, the rest of the composition, by flour, dried chicory (dehydrated), and salts, vitamins and minerals. The dried chicory, is in the form of an extract of chicory, made in accordance with a form of presentation of this invention, and that is added in an amount corresponding to a percentage of about 5%, or less. Food mix, it is introduced in a pre-conditioner, and it gelatinizes The gelatinized matrix, when leaving the extruder, it is forced to make it pass through a matrix, and it is thwarted, thus forming an extrudate. The extruded, is cut into pieces or "cubes", appropriate for feeding dogs, it is dried at a temperature of approximately 110 ° C, during a time course of approximately 20 minutes, and at then it cools to form granules. It should be appreciated the fact that, part or all of the fat matrix, or the grease and oil used, can be added in one stage later, for example, as a coating.

Added chicory, can improve the health of companion or domestic animals, proceeding, for example, to prevent and / or treat inflammation, as discussed above

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Example 2

Dry food product (dehydrated), for animals of company

A food product is prepared dry (dehydrated), for pets or pets, of the same form as the food product for pets or company example 1. This additionally includes a additional ingredient typically associated with the improvement of appetite or taste of the animal food product domestic or companion, appropriate for cats. Chicory added, it can improve the health of the pet or companion, for example, preventing and / or treating inflammation, as it is He has discussed above, above.

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Example 3

Dry food product (dehydrated), for cats

It proceeds to form a food mixture, to basis of approximately 58%, by weight, of corn, approximately a percentage of 6%, by weight, of corn gluten, approximately 23%, by weight, of chicken meal, being formed, the rest of the composition, by chicory dried (dehydrated), and salts, vitamins and minerals. Chicory dry, is added in an amount corresponding to a percentage of approximately 5% or less. As discussed previously, above, the added chicory, can inhibit the Enzymatic activity, which is believed to improve health in the animal, for example, treating and / or preventing inflammation.

The food mixture is introduced into a pre-conditioner and moistened. The moistened matrix, when exiting the extruder, is forced to pass it through a matrix, and is extruded, thus forming an extrudate. The extrudate is cut into pieces or "cubes", suitable for feeding cats, dried at a temperature of approximately 110 ° C, over a period of approximately 20 minutes, and then cooled, to form granules. In this state, a lyophilized powder material of one or more strains of the Lactobacillus species, such as Lactobacillus rhammosus NCC2583 (CNCM I-2449), Lactobacillus acidophilus NCC2628 (CNCM I-2453) is applied to the granules. and Enterococcus faecium SF68 (NCIMB 10415). To the granules, a sufficient amount of powdered matter is applied, so that the corresponding amount of dietary intake, for the cat, is corresponding to values within ranges ranging from about 1.0 E + 0.7 to 1.0 E + 9 cfu / day. In this sense, a portion of the powdered material is mixed in a first mass of granules, which are subsequently packed. A second portion of the powdered material is measured and mixed with a liquid carrier or support, which is then sprayed onto a second mass of the granules. The granules are packed, after the coating has dried sufficiently, at a temperature of 50-60 ° C, over a period of a few seconds.

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Example 4

Food product and supplement, canned, for animals domestic

We proceed to prepare a mixture based approximately a percentage of 73% of carcasses of poultry, pork lungs and veal liver (ground), approximately one percentage of 16% wheat flour, approximately one 2% percentage of dyes, vitamins and inorganic salts. This mixture, is emulsified at a temperature of 12 ° C and extruded, conforming it in the form of a flan or pudding. The emulsion will be add dried chicory (dehydrated), in the form of an extract carried out in accordance with a form of presentation of the present invention, in an amount corresponding to a percentage 5% or less. The emulsion is then cooked, to a temperature of 90 ° C. This is cooled to a temperature of 30 ° C and, It is then cut into pieces or "cubes." Approximately 45% of the pieces or cubes are mix with approximately a 55% percentage of the sauce, the which is prepared from a percentage of approximately 98% of water, a percentage of approximately 1% dye, and a percentage of about 1% guar gum. Proceed to fill tin cans with the mixture of the pieces or "cubes" and the sauce, and it is sterilized at a temperature of 125 ° C, over a period of approximately 40 minutes

As a prebiotic supplement to be mixed with the food product for pets or pets, before serving, an additional packaging is provided, in the form of a sachet, with strains of the following Lactobacillus species, Lactobacillus rhammosus NCC2583 (CNCM I-2449 ), Lactobacillus acidophilus NCC2628 (CNCM I-2453) or Enterococcus faecium SF68 (NCIMB 10415). The corresponding dietary intake of the supplement, for the pet or companion animal, is from about 106-1012 cfu / day, depending on the type of pet or companion animal, for example, a cat or a dog , and of the physical factors of pet or companion, such as body mass. The supplement is packaged in such a way that it is attached to the can, in a non-disposable way, together with the directions of the food.

By way of example, and not limitation, proceeded to carry out an experimental test test, as It is described in detail, below, below, to demonstrate the effectiveness of the present invention.

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In vitro test test 1

The inventors have carried out a certain number of experimental test tests, to demonstrate  the beneficial effects of the present invention. In a way In general, cultures of human colon cancer were prepared, and treated with varying amounts of chicory extracts, during a time course of approximately 48 hours, to evaluate the effects of chicory, with respect to activity cyclooxygenase The preparation and testing procedures of Experimental trials, as well as the results, are discussed below, then in greater detail.

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Preparation of cell culture

An HT 29 cancer cell line was obtained of colon, of the American Type Culture Collection, and cultivated in McCoy medium 5A, supplemented with 10% fetal bovine serum (FBS), 25 mg / ml gentamicin. HT-29 cells, they were treated with a certain number of different extracts of chicory, made in accordance with a form of presentation of the present invention, as detailed below, to continuation.

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Preparation of chicory extracts

Four extracts were prepared different from chicory, namely the A-D extracts, in accordance with a form of presentation of this invention. Initially, it was screened, to a size of 0.5 mm, a sample of 40 grams (g) and a sample of 10 g, of Chicory, ground to a powdered form. The samples are processed, to remove the fats, proceeding to mix the samples, with hexane, over a period of time of approximately thirty minutes, at room temperature. Be He then added 600 milliliters (ml) of hexane, to the sample of chicory sieved, of 40 g, and 150 ml were added, to the screened sample of 10 g. Hexane, evaporated, under the action from vacuum, at a temperature of about 50 ° C, to form Extract A.

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Extract B, was prepared, proceeding, in first, to defat 40 grams of ground chicory, in powder, in the manner discussed above, above. The degreased sample, hydrolyzed in 300 ml of an acid, such as HCl, in a hot water bath, over a period of time approximately 20 minutes After cooling and proceed to the centrifugation (8000 revolutions per minute, 5 minutes, 10 ° C), the solution, extracted with 150 ml of a solvent, such as the ethyl acetate, which is commercially available in the market, for example, from the MERCK firm. He solvent, evaporates until dried. After proceeding to dry additionally, in anhydrous sodium sulfate, under the action of vacuum, at a temperature of about 50 ° C, the extract B.

Extracts C and D, were prepared from the following form. First, we proceeded to degrease 10 grams sample of ground chicory powder, in the way described above, with an amount of approximately 250 ml of a solvent / water mixture, such as the consisting of a ratio value, based on weight, of MeOH and water in solution. The extraction is carried out under the action of stirring, at room temperature (for example, at temperature within a range of about 20 ° C to about 25 ° C), over a course of time of approximately 30 minutes. After the centrifugation, the solution, is divided into two equal parts in volume. In the first part by volume of the solution, the organic solvent, evaporates, under the action of vacuum, at a temperature of about 50 ° C. The remaining aqueous phase is freeze-dried (freeze-dried, to form the extract C.

The second part by volume of the solution is treat with approximately 2 g of polyvinylpyrrolidone, under the stirring action, over a period of time of approximately 30 minutes, to trap the polyphenols. He adsorbent material, is removed, by filtration, centrifugation, or the like. The organic solvent evaporates under the action of vacuum, at a temperature of approximately 50 ° C. The remaining aqueous phase is dried by freezing (it is lyophiliza), to form extract D.

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PGE2 production measurement

We proceeded to analyze the effects of several chicory extracts, namely the A-C extracts, in the biosynthesis of PGE2, in a human colon cell line HT29 The biosynthesis of PGE2 provides the indication of the level of the enzymatic activity, such as cyclooxygenase, since, such and as is generally known, cyclooxygenase, can act as a catalyst to produce PGE2 from, by example, arachidonic acid. Thus, in this way, the effects of chicory extract, in the enzymatic activity of the cyclooxygenase, can be evaluated, based on this experiment, as and as described below, below.

The cells were grown during a 48-hour time course, in your environment, supplemented with a 0.1% percentage of bovine serum albumin (BSA) and acid 10 µM arachidonic. Chicory extracts were added to then, to this medium, at a concentration of 50, 100 and 200 ? / ml, over a period of time of either 21 hours, or good 15 hours. We proceeded to prepare another set of samples of cells, adding chicory extract B, to the cells HT-29, as discussed above, followed by a co-incubation, in the presence of 10 ng / ml factor tumor necrosis alpha (TNF), over a period of 6 hours. It is generally believed that the TNF, It will stimulate inflammation.

The quality of the PGE2 was determined, in cellular medium, with the equipment, as a kit, of immunoassay of monoclonal enzyme PGE2 (from Cayman Chemical), in concordance with the manufacturer's instructions. In short, it proceeded to mix 25 or 50 µl of the medium, together with standard samples of PGE2 as standard, diluted, with a quantity appropriate tracer labeled with acetylcholine stearase and antiserum of PGE2, and incubated at room temperature, during a 18 hour time course. After the holes are They had emptied and washed with wash buffer, we proceeded to add 200 µl of Ellman reagent, which contained the substrate for acetylcholine stearase. The reaction of the enzymes, led to out on a slow stirrer, at room temperature, for a 1 hour time course. The results were measured proceeding to use a microplate reader, at 415 nm, and it normalized to micrograms of protein.

The results of the test test indicated the fact that, chicory extract B, which was performed with ethyl acetate, as discussed above, above, had the most pronounced effect, in the inhibition of activity cyclooxygenase, as evidenced by a decrease of the measured amount of PGE2. In a general way, the decrease in cyclooxygenase activity, it was more pronounced with amounts chicory extract increments. Additionally, in addition, test test results indicated the fact that the chicory extract B, had a more pronounced effect, in the inhibition of cyclooxygenase activity, in the cell line HT-29 with TNF, if compared to the cell line HT-29, without TNF. This suggests the fact that, the cyclooxygenase activity, may be more influenced by a specific inhibition of cyclooxygenase-2, if compare with cyclooxygenase-1. The results obtained, are presented in table 1, which is provided to continuation.

TABLE 1 Effect of chicory extracts with acetate ethyl, in the synthesis of PGE-2, in cells HT-29

one

* Stimulation of enzymatic activity, using TNF-alpha, it was 10 times higher.

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In vitro test test 2 1. Inhibitory effects of α-CH2-? -butyrolactone, in the synthesis of PGE2

The inventors have carried out a test of similar experimental trial, to demonstrate the effects anti-inflammatory of the alpha-methylene-gamma-butyrolactone. In general, synthesis inhibition has been demonstrated of PGE2, through alpha-methylene-gamma-butyrolactone, in HT29 cells, stimulated by TNF-alpha. With for this purpose, cells were cultured, and these were made pass in a 5A medium of Mc Coy, supplemented with arachidonic acid (10 microliters) and bovine serum albumin (0.01%). The cells are they tried by alpha-methylene-gamma-butyrolactone (dissolved in methanol), at the following doses: 15, 30, 60 microM or by the solvent alone, over a period of 21 hours, including stimulation with TNF-alpha (10 ng / ml), over a period of 6 hours, or not including it. PGE2 analysis was performed using a test. ELISA test, in a sample of medium.

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TABLE 2 PGE2 concentration, in pg / ml, of medium in HT29 cells, treated with α-CH 2 - γ-butyrolactone, with TNF-?, or without it

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2

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2. Inhibitory effects of α-CH 2 - γ-butyrolactone, in the expression of COX-2 Western transfer analysis

Cell lysates were prepared, treating HT29 cells (treated in the manner described above, above, for PGE2 determinations, that is, in the presence of TNF-alpha and with or without α-CH 2 - γ-butyrolactone),  with lysis buffer (150 mM NaCl, 10 mM Tris HCl pH 8.1% Tween 20, EDTA pH 8 1mM, protease inhibitors, PEFA, (Merck), DETEC (Aldrich) The lysates were sonified (treated with ultrasound), over a period of 5 seconds, and centrifuged at 10,000 g for a period of 5 minutes The protein concentration was estimated, using the Bradford method, which was standardized, using bovine serum albumin.

The whole of the boils were boiled cell extracts (25 µg), in Laemmli sample buffer, and dissolved, again, by SDS-PAGE, in 10% gel, using the gel batch system polyacrylamide Non-specific binding sites were blocked, proceeding to block the membrane in buffered saline solution of 5% lactic phosphatase, which contained 0.1% of Tween-20, during the course of the night, to a temperature of 4 ° C.

The eruptions, hybridized in a dilution 1 : 1000, of polyclonal anti COX-2 antibody and also COX-1, goat (C-20, Santa Cruz Biotechnology), in 5% milk PBS), during one course of time of 1 hour, at room temperature, followed by a washed over a period of 1 hour, in 1% PBS dairy.

Subsequently, the eruptions were tested with a secondary anti-goat antibody conjugate of donkey and horseradish peroxidase. After proceeding to wash over a period of 1 hour, the complex, using Western blot reagents of ECL (Amersham).

The results obtained are shown in the Figure 1.

3. Specific inhibition of activity COX-2, through α-CH 2 - γ-butyrolactone

The team as a "kit" of the activity of Stressgen StressXpress® cyclooxygenases, provides a procedure to specifically measure cyclooxygenases COX-1 and COX-2, in a variety of biological fluids The equipment as a "kit" uses a specific chemiluminescent substrate (hydrocarbon molecule aromatic), to detect the peroxidase activity of COX enzymes. After inhibition by specific compounds (α-CH 2 - γ-butyrolactone and NS-938, a COX-2 inhibitor from the Cayman Chemical Company, both dissolved in methanol), the residual activity of the cyclooxygenase, by adding chemiluminescent substrate and arachidonic acid (50 µM). The light emission starts immediately and the chemiluminescent signal is measured (Relative Luminisecence Units - RLU - [Luminescence Units relative] -), after a period of 30 minutes (Tecan luminometer). The amount of light emitted is directly proportional to COX activity.

In this test test, it was found that,                                         the α-CH 2 - γ-butyrolactone, specifically inhibited, and with great power, activity COX-2, just as the compound did NS-398 reference. The results obtained are they represent in table 3.

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TABLE 3 Measurement of cyclooxygenase activities (COX-1, COX-2)

3

Claims (12)

1. A composition comprising an extract of extruded chicory, thermally processed, which comprises sesquiterpene lactose, which comprise α-methylene- γ-butyrolactone (? -MGBL), where, the extract of chicory, is obtained by degreasing the plant material of chicory, to form a first plant extract and, subsequently processing the first floor, using the first plant extract, using acid hydrolysis and a solvent extraction, with ethyl acetate, to form the chicory extract. 2. A composition according to claim 1, which includes an effective amount of one or more photochemical agents,  which include a sesquiterpene lactone, which has, as active fragment, α-methylene-γ-butyrolactone. 3. A composition, according to any one of the claims 1 to 2, wherein the composition comprises a 0.5% percentage, by weight, of chicory extract. 4. A composition, according to any one of the preceding claims, which further comprises a dietary agent, selected from the group consisting of antioxidants, glucosaline, coindritin sulfate, fatty acids omega-3, and combinations of these. 5. A food product, which is a food product for pets, comprising: a starch matrix; Y a composition according to any one of the claims 1 to 4. 6. A food product, according to the claim 5, selected from the group consisting of a nutritional supplement, a nutritiously complete product, a food product preparation, a cereal product, a product for pets, and a food preparation Pharmaceutical and / or functional. 7. A procedure to prepare a product nutritional food, for the prevention and / or treatment of inflammation in a mammal, comprising the procedure, the stages of: provide a chicory extract, obtained by degreasing chicory plant material, to form a first plant extract and subsequently process the first plant extract, using acid hydrolysis and solvent extraction, with ethyl acetate, to form a chicory extract, and process the chicory extract and one or more food ingredients, to form a food product nutritious, which includes, at least, a percentage of 0.5%, in weight of chicory extract. 8. A method according to claim 7, in which, chicory extract, includes one or more agents photochemicals, capable of inhibiting the enzymatic activity of the cyclooxygenase and / or the transcriptional factor of NF-KB 9. A method according to claim 7 or 8, in which, ground chicory extract, includes additionally a dietary agent selected from the group consisting of antioxidants, glucosamine, fatty acids omega-3 or a combination of these. 10. A composition, according to any one of the claims 1 to 4, for use in therapy. 11. Use of a composition according to any one of claims 1 to 4, in the manufacture of a medicament for use in the treatment of inflammation or cancer, or for reduce the risk of inflammation, of osteoarthritis, of a autoimmune or cancer disease, in a mammal. 12. Use according to claim 11, wherein the medicine comprises a percentage of 0.5%, by weight, of a composition according to any one of claims 1 to 4.